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Reproductive toxicity of an estrogenic polyfluoroalkyl substance on fathead minnows
Citation:
Collins, J., G. Ankley, B. Blackwell, C. Blanksma, J. Cavallin, M. Ellman, J. Hoang, K. Jensen, M. Kahl, K. Santana Rodriguez, C. Schaupp, P. Shankar, E. Stacy, AND D. Villeneuve. Reproductive toxicity of an estrogenic polyfluoroalkyl substance on fathead minnows. SETAC North America, 44th Annual Meeting, Louisville, KY, November 12 - 16, 2023. https://doi.org/10.23645/epacomptox.29041916
Impact/Purpose:
Per and polyfluoroalkyl substances (PFAS) are a large class of chemicals of concern to the agency due to their widespread use, persistence in the environment, and potential for exposure and effects in humans and wildlife. Alternatives to traditional animal testing, termed new approach methodologies (NAMs) are being used to generate information on potential hazards of previously untested PFAS. However, for these data to be used for risk assessment and regulatory decision-making, it is important to establish their relevance for predicting in vivo hazards. The present work verifies that a PFAS identified as an estrogenic endocrine disruptor through in vitro screening is able to elicit estrogenic activity in vivo and associated adverse effects on reproduction. The results provide both increased confidence in the NAMs-based hazard screening approach, and provide points of departure for use in screening level assessments. As such, this research helps support OCSPP, OLEM, OW, and the Regions as they work to regulate PFAS in the environment.
Description:
In previous studies, male fathead minnows (Pimephales promelas) were exposed to four PFAS that were shown to have estrogenic activity in vitro. Based on results from these 4 d in vivo tests, 1H,1H,10H,10H-Perfluorodecane-1,10-diol (FC10-diol) (DTXID50369896) was found to be the most estrogenically-potent among the tested chemicals. Therefore, FC10-diol was selected to evaluate whether estrogenic PFAS could elicit responses consistent with a hypothesized adverse outcome pathway (AOP) linking estrogen receptor agonism to reproductive impairment in fish. To determine the robustness of the AOP and potential reproductive toxicity of FC10-diol, adult fathead minnows were exposed for 21 days to one of five nominal concentrations of FC10-diol (0.68; 2.1; 6.8; 21; or 68 µg/L) or E2 (1 µg/L) in a short-term reproduction assay. Estrogen receptor activation was again confirmed as estrogen-regulated genes were up-regulated (vtg and esr1) or down-regulated (igf1 and apoeb) in a concentration-dependent manner in exposed males. Morphologically, FC10-diol reduced male secondary sex characteristics as reflected by a reduction in tubercle score and, at the highest dose of FC10-diol, both male and female fathead minnows experienced a reduction in gonadosomatic index (GSI). A hypothesized increase in oocyte atresia in exposed females was confirmed histologically by a significant increase in the incidence and severity oocyte atresia in females exposed to the high dose of FC10-diol. Cumulative fecundity was significantly reduced for fish exposed to either 6.8 or 68ug/L of FC10-diol. The results of this study verify both the reproductive toxicity of FC10-diol in vivo and the applicability of the hypothesized AOP for estrogenic PFAS. The contents of this abstract neither constitute, nor necessarily reflect US EPA policy.
URLs/Downloads:
DOI: Reproductive toxicity of an estrogenic polyfluoroalkyl substance on fathead minnows
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